The Role of Hydrogen Sulfide in Respiratory Diseases.
Ontology highlight
ABSTRACT:
SUBMITTER: Khattak S
PROVIDER: S-EPMC8147381 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Despite an obnoxious smell and toxicity at a high dose, hydrogen sulfide (H2S) is emerging as a cardioprotective gasotransmitter. H2S mitigates pathological cardiac remodeling by regulating several cellular processes including fibrosis, hypertrophy, apoptosis, and inflammation. These encouraging findings in rodents led to initiation of a clinical trial using a H2S donor in heart failure patients. However, the underlying molecular mechanisms by which H2S mitigates cardiac remodeling are not completely understood. Empirical evidence suggest that H2S may regulate signaling pathways either by directly influencing a gene in the cascade or interacting with nitric oxide (another cardioprotective gasotransmitter) or both. Recent studies revealed that H2S may ameliorate cardiac dysfunction by up- or downregulating specific microRNAs. MicroRNAs are noncoding, conserved, regulatory RNAs that modulate gene expression mostly by translational inhibition and are emerging as a therapeutic target for cardiovascular disease (CVD). Few microRNAs also regulate H2S biosynthesis. The inter-regulation of microRNAs and H2S opens a new avenue for exploring the H2S-microRNA crosstalk in CVD. This review embodies regulatory mechanisms that maintain the physiological level of H2S, exogenous H2S donors used for increasing the tissue levels of H2S, H2S-mediated regulation of CVD, H2S-microRNAs crosstalk in relation to the pathophysiology of heart disease, clinical trials on H2S, and future perspectives for H2S as a therapeutic agent for heart failure.
| S-EPMC4867357 | biostudies-literature
Project description:Endothelial cells are important constituents of blood vessels that play critical roles in cardiovascular homeostasis by regulating blood fluidity and fibrinolysis, vascular tone, angiogenesis, monocyte/leukocyte adhesion, and platelet aggregation. The normal vascular endothelium is taken as a gatekeeper of cardiovascular health, whereas abnormality of vascular endothelium is a major contributor to a plethora of cardiovascular ailments, such as atherosclerosis, aging, hypertension, obesity, and diabetes. Endothelial dysfunction is characterized by imbalanced vasodilation and vasoconstriction, elevated reactive oxygen species (ROS), and proinflammatory factors, as well as deficiency of nitric oxide (NO) bioavailability. The occurrence of endothelial dysfunction disrupts the endothelial barrier permeability that is a part of inflammatory response in the development of cardiovascular diseases. As such, abrogation of endothelial cell activation/inflammation is of clinical relevance. Recently, hydrogen sulfide (H2S), an entry as a gasotransmitter, exerts diverse biological effects through acting on various targeted signaling pathways. Within the cardiovascular system, the formation of H2S is detected in smooth muscle cells, vascular endothelial cells, and cardiomyocytes. Disrupted H2S bioavailability is postulated to be a new indicator for endothelial cell inflammation and its associated endothelial dysfunction. In this review, we will summarize recent advances about the roles of H2S in endothelial cell homeostasis, especially under pathological conditions, and discuss its putative therapeutic applications in endothelial inflammation-associated cardiovascular disorders.
| S-EPMC6985156 | biostudies-literature
Project description:Hydrogen sulfide (H2S) is a gasotransmitter that acts as an antioxidant and exhibits a wide variety of cytoprotective and physiological functions in age-associated diseases. One of the major causes of age-related diseases is oxidative stress. In recent years, the importance of H2S has become clear, although its antioxidant function has not yet been fully explored. The enzymes cystathionine ?-synthase, cystathionine ?-lya-se, and 3-mercaptopyruvate sulfurtransferase are involved in the enzymatic production of H2S. Previously, H2S was considered a neuromodulator, given its role in long-term hippocampal potentiation, but it is now also recognized as an antioxidant in age-related neurodegeneration. Due to aerobic metabolism, the central nervous system is vulnerable to oxidative stress in brain aging, resulting in age-associated degenerative diseases. H2S exerts its antioxidant effect by limiting free radical reactions through the activation of antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase, which protect against the effects of aging by regulating apoptosis-related genes, including p53, Bax, and Bcl-2. This review explores the implications and mechanisms of H2S as an antioxidant in age-associated neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and Down syndrome.
| S-EPMC6975154 | biostudies-literature
Project description:Hydrogen sulfide has gained recognition as the third gaseous signaling molecule after nitric oxide and carbon monoxide. This review surveys the emerging role of H2S in mammalian renal system, with emphasis on both renal physiology and diseases. H2S is produced redundantly by four pathways in kidney, indicating the abundance of this gaseous molecule in the organ. In physiological conditions, H2S was found to regulate the excretory function of the kidney possibly by the inhibitory effect on sodium transporters on renal tubular cells. Likewise, it also influences the release of renin from juxtaglomerular cells and thereby modulates blood pressure. A possible role of H2S as an oxygen sensor has also been discussed, especially at renal medulla. Alternation of H2S level has been implicated in various pathological conditions such as renal ischemia/reperfusion, obstructive nephropathy, diabetic nephropathy, and hypertensive nephropathy. Moreover, H2S donors exhibit broad beneficial effects in renal diseases although a few conflicts need to be resolved. Further research reveals that multiple mechanisms are underlying the protective effects of H2S, including anti-inflammation, anti-oxidation, and anti-apoptosis. In the review, several research directions are also proposed including the role of mitochondrial H2S in renal diseases, H2S delivery to kidney by targeting D-amino acid oxidase/3-mercaptopyruvate sulfurtransferase (DAO/3-MST) pathway, effect of drug-like H2S donors in kidney diseases and understanding the molecular mechanism of H2S. The completion of the studies in these directions will not only improves our understanding of renal H2S functions but may also be critical to translate H2S to be a new therapy for renal diseases.
| S-EPMC5067532 | biostudies-literature
Project description:Hydrogen sulfide (H2S) is a gaseous signaling molecule produced in the body by three enzymes: cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST). H2S is crucial in various physiological processes associated with female mammalian reproduction. These include estrus cycle, oocyte maturation, oocyte aging, ovulation, embryo transport and early embryo development, the development of the placenta and fetal membranes, pregnancy, and the initiation of labor. Despite the confirmed presence of H2S-producing enzymes in all female reproductive tissues, as described in this review, the exact mechanisms of H2S action in these tissues remain in most cases unclear. Therefore, this review aims to summarize the knowledge about the presence and effects of H2S in these tissues and outline possible signaling pathways that mediate these effects. Understanding these pathways may lead to the development of new therapeutic strategies in the field of women's health and perinatal medicine.
| S-EPMC11202402 | biostudies-literature
Project description:Ischemia-reperfusion (I/R) injury is one of the major causes of high morbidity, disability, and mortality in the world. I/R injury remains a complicated and unresolved situation in clinical practice, especially in the field of solid organ transplantation. Hydrogen sulfide (H2S) is the third gaseous signaling molecule and plays a broad range of physiological and pathophysiological roles in mammals. H2S could protect against I/R injury in many organs and tissues, such as heart, liver, kidney, brain, intestine, stomach, hind-limb, lung, and retina. The goal of this review is to highlight recent findings regarding the role of H2S in I/R injury. In this review, we present the production and metabolism of H2S and further discuss the effect and mechanism of H2S in I/R injury.
| S-EPMC4443900 | biostudies-other
Project description:Hydrogen sulfide (H2S) is one of the important biological mediators involved in physiological and pathological processes in mammals. Recently developed H2S donors show promising effects against several pathological processes in preclinical and early clinical studies. For example, H2S donors have been found to be effective in the prevention of gastrointestinal ulcers during anti-inflammatory treatment. Notably, there are well-established medicines used for the treatment of a variety of diseases, whose chemical structure contains sulfur moieties and may release H2S. Hence, the therapeutic effect of these drugs may be partly the result of the release of H2S occurring during drug metabolism and/or the effect of these drugs on the production of endogenous hydrogen sulfide. In this work, we review data regarding sulfur drugs commonly used in clinical practice that can support the hypothesis about H2S-dependent pharmacotherapeutic effects of these drugs.
| S-EPMC7072623 | biostudies-literature
Project description:Hydrogen sulfide (H2S) is a naturally occurring gas that is also associated with several industries. The potential for widespread human inhalation exposure to this toxic gas is recognized as a public health concern. The nasal epithelium is particularly susceptible to H2S-induced pathology. Injury to and regeneration of the nasal respiratory mucosa occurred in animals with ongoing H2S exposure suggesting that the regenerated respiratory epithelium undergoes an adaptive response and becomes resistant to further H2S induced toxicity. To better understand this adaptive response, twenty-four naive 10-week old male Sprague-Dawley rats were exposed to air or 200 ppm H2S in a nose-only exposure system for 3h/d for 1 or 5 consecutive days. Nasal respiratory epithelial cells at the site of injury and regeneration were laser capture microdissected and gene expression profiles were generated at time 3h, 6h, 24h, and 144h post initial exposure using the Affymetrix Rat Genome 430 2.0 microarray. Gene ontology enrichment analysis identified early gene changes in such functional categories as signal transduction, inflammatory/defense response, cell cycle, and response to oxidative stress. Later gene changes occurred in categories involved in cell cycle, DNA repair, transport, and micro-tubule-based movement. These data contribute to our understanding of the nasal epithelial cells? response to inhaled environmental toxicants. A better understanding of the H2S cytotoxicity mechanism will improve human risk assessment. Keywords: Time course
2008-07-01 | GSE5349 | GEO
Project description:Respiratory syncytial virus (RSV) can cause severe respiratory illness in infants, immunocompromised, and older adults. Despite its burden, no vaccine or specific treatment is available. RSV infection is associated with increased reactive oxygen species (ROS) production, degradation of the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2), and decreased antioxidant enzymes (AOEs), leading to oxidative damage and lung injury. Hydrogen sulfide (H2S) is an endogenous gaseous molecule that plays a physiological role in numerous cellular processes and a protective role in multiple pathological conditions, displaying vasoactive, cytoprotective, anti-inflammatory, and antioxidant activities. H2S can promote NRF2 activation through the sulfhydration of Kelch-like ECH-associated protein 1, the cytoplasmic repressor of NRF2. Here we investigated whether increasing cellular H2S levels could rescue NRF2 and NRF2-dependent gene expression in RSV-infected primary airway epithelial cells. We found that treatment with the H2S donor GYY4137 significantly increased NRF2 levels and AOEs gene expression by decreasing KEAP1 levels, and by modulating pathways involved in RSV-induced NRF2 degradation, such as NRF2 ubiquitination, and promyelocytic leukemia (PML) protein levels. These results suggest that the administration of exogenous H2S can positively impact the altered redox balance associated with RSV infection, which represents an important determinant of RSV-induced lung disease.
| S-EPMC9311616 | biostudies-literature
Project description:Hydrogen sulfide (H2S) is a naturally occurring gas that is also associated with several industries. The potential for widespread human inhalation exposure to this toxic gas is recognized as a public health concern. The nasal epithelium is particularly susceptible to H2S-induced pathology. Injury to and regeneration of the nasal respiratory mucosa occurred in animals with ongoing H2S exposure suggesting that the regenerated respiratory epithelium undergoes an adaptive response and becomes resistant to further H2S induced toxicity. To better understand this adaptive response, twenty-four naive 10-week old male Sprague-Dawley rats were exposed to air or 200 ppm H2S in a nose-only exposure system for 3h/d for 1 or 5 consecutive days. Nasal respiratory epithelial cells at the site of injury and regeneration were laser capture microdissected and gene expression profiles were generated at time 3h, 6h, 24h, and 144h post initial exposure using the Affymetrix Rat Genome 430 2.0 microarray. Gene ontology enrichment analysis identified early gene changes in such functional categories as signal transduction, inflammatory/defense response, cell cycle, and response to oxidative stress. Later gene changes occurred in categories involved in cell cycle, DNA repair, transport, and micro-tubule-based movement. These data contribute to our understanding of the nasal epithelial cells? response to inhaled environmental toxicants. A better understanding of the H2S cytotoxicity mechanism will improve human risk assessment. Experiment Overall Design: Twenty-four naive 10-week old male Sprague-Dawley rats were exposed to air or 200 ppm H2S in a nose-only exposure system for 3h/d for 1 or 5 consecutive days. Nasal respiratory epithelial cells at the site of injury and regeneration were laser capture microdissected and gene expression profiles were generated at time 3h, 6h, 24h, and 144h post initial exposure using the Affymetrix Rat Genome 430 2.0 microarray.
2009-10-18 | E-GEOD-5349 | biostudies-arrayexpress